In man, there exists not only pancreatic phospholipase A.sub.2 (PLA.sub.2) (type I) but also membrane-bound and secretion type phospholipase A.sub.2 (type II). These types of phospholipase A.sub.2 are widely divergent in biochemical properties.
Among them, pancreatic phospholipase A.sub.2 is one of the digestive enzymes synthesized in the pancreas and secreted into pancreatic juice. Pancreatic phospholipase A.sub.2 is activated by trypsin, a proteolytic enzyme, in the duodenum and decomposes the phospholiplds blended with the bile and solubilized. While pancreatic phospholipase A.sub.2 readily decomposes the cell membrane comprised of phospholipids, the lyso compounds produced in this process show high cytotoxicity. Therefore, pancreatic phospholipase A.sub.2 has been a focus of attention in connection with the onset and exacerbation of acute pancreatitis. It is generally postulated that since, in man, there is no inhibitor of pancreatic phospholipase A.sub.2 activity, pancreatic phospholipase A.sub.2 finds its way into the circulation at the acme of pancreatitis to induce severe cytopatic effects. As a drug having such a pharmacologic action, citicholine is known.
Meanwhile, type II phospholipase A.sub.2 (non-pancreatic type) which is detected at high levels in the exudates at inflammation sites is generally considered to be deeply involved in inflammation. The mechanism of its inflammatory actions is generally visualized as the type II phospholipase A.sub.2 -catalyzed production of arachidonic acid from the phospholipids of, for example, the cell membrane which is followed by both the cyclooxygenase pathway leading to prostaglandines (PG) and the lypoxygenase pathway leading to leukotrienes (LT). Steroidal drugs are known to inhibit type II phospholipase A.sub.2 and, hence act as antiinflammatory agents blocking both of the pathways.
Thus, type I and type II phospholipase A.sub.2 are much different in biochemical properties but in the field of medicine there is not known a drug which sufficiently inhibits both of type I phospholipase A.sub.2 which is associated with pancreatitis and type II phospholipase A.sub.2 (non-pancreatic type) which is involved in inflammation.
Paying attention to inhibition of pancreatic phospholipase A.sub.2, the inventors of this invention did intensive research. As a result, they discovered that an ascorbyl tocopheryl phosphate compound which is already known as an antiinflammatory agent having phospholipase A.sub.2 inhibitory activity (U.S. Pat. No. 4,914,197) is of value as a therapeutic drug for pancreatitis by virtue of its pancreatic phospholipase A.sub.2 inhibitory action. This invention has been developed on the basis of the above finding.
This invention provides a very useful therapeutic composition for pancreatitis which comprises a phosphoric diester compound or a pharmacologically acceptable salt thereof.